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Anticonvulsant Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Zonisamide is an anticonvulsant used either in monotherapy or in polytherapy to treat a broad spectrum of epileptic conditions (Oguni et al., 1988; Schmidt et al., 1993). In a small prospective case series of 26 infants born to women treated throughout pregnancy with zonisamide as part of a polytherapy anticonvulsant regimen, two infants (7.7 percent) were reported with major congenital anomalies (anencephaly, atrial septal defect) (Kondo et al., 1996). A child whose mother took zonisamide, carbamazepine, phenytoin, sodium valproate, and a barbiturate during pregnancy was reported with features of anticonvulsant embryopathy (Noda et al., 1996).
Medicines in neonates
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
EIEE is characterised by a very early onset, frequent tonic spasms and suppression-burst pattern in the EEG. Most cases are associated with structural brain damage. Treatment is disappointing, although ACTH and/or corticosteroids are occasionally helpful [36]. Other agents (vitamin B6 and sodium valproate) have also been used. The possible role of new AEDs has not been assessed. One case treated with zonisamide has been reported [37], and some cases were treated surgically.
Epilepsy
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Donald C. Barr, Andres M. Kanner
Available data on the teratogenic potential are limited to first- and second-generation ASDs, while those of third-generation drugs are yet to be established. First-line therapy consists of monotherapy with either lamotrigine or levetiracetam, irrespective of seizure type. Data from the North American ASD Pregnancy Registry and the International Registry of ASDs in Pregnancy (EURAP) placed lamotrigine and levetiracetam among the AEDs with the lowest rates of major cortical malformations (MCMs) at 2.0–2.9% and 2.4–2.8%, respectively, comparable to rates reported among healthy women on no medications.62,63 Among the other ASDs considered to be safe during pregnancy, oxcarbazepine has a 2.6–3% risks of MCMs,63 while zonisamide can also be considered, but it carries a risk of small-for-gestational-age for the neonate.63,64
Current safety concerns about the use of antiseizure medications in pregnancy
Published in Expert Opinion on Drug Safety, 2022
Giovanni Falcicchio, Emilio Russo, Antonio Fabiano, Micaela Scalese, Giovanni Boero, Maria Trojano, Marina de Tommaso, Angela La Neve
A change in prescribing practice has also been reported in a study analyzing data collected by UKIEPR on pregnancies from 1996 to 2016 [52]. The change, in favor of the less teratogenic medications (levetiracetam and lamotrigine), concerns the choice of monotherapy agent. The authors reported an overall reduction in MCMs, albeit not significant [52]. Results from a small-scale study using data from the same registry raised concern about the use of zonisamide during pregnancy [53]. Between 1996 and 2020, 112 women took zonisamide in mono- (n = 26) or polytherapy (n = 86) during the first trimester of pregnancy. The number of live births was 21/26 (81%) in the monotherapy group versus 70/86 (81%) in the polytherapy cases. Three MCMs were identified in the monotherapy group (MCM rate = 13%) and five in the polytherapy group (MCM rate = 6.9%). These results must be interpreted with caution given that, among the five cases of MCMs in the polytherapy group, four of the mothers were simultaneously taking topiramate or valproate (known to be teratogenic) [53]. In our opinion, these data cannot be transferred to clinical practice.
Current understanding of the etiology of cyclic vomiting syndrome and therapeutic strategies in its management
Published in Expert Review of Clinical Pharmacology, 2022
Rosita Frazier, Thangam Venkatesan
fSalvage therapy with zonisamide or levetiracetam has also been reported. Zonisamide is a sulfonamide anticonvulsant which binds to sodium and voltage-sensitive calcium channels, preventing depolarization and hypersynchronization in neurons [71]. The mechanism of action of levetiracetam has not yet been completely elucidated, however it is known to block presynaptic calcium channels by binding to SV2A, a synaptic vesicle glycoprotein, limiting neurotransmitter release and serving as a neuromodulator [72]. A study by Clouse et al. using either zonisamide or levetiracetam in patients with CVS who failed to respond to TCA therapy showed that 75% had a moderate clinical response, while 20% experienced a complete response with cessation of CVS episodes at a mean follow-up of 9.5 months [73]. Zonisamide usually starts at 100 mg daily and is slowly titrated up to 400 mg daily. Common side effects included fatigue, dizziness, decreased appetite, headache, agitation, or irritability [74]. The target dose for levetiracetam target dose is 1000–2000 mg daily, but it usually starts at 500 mg daily and then increases by 500 mg each week. Common side effects include dizziness, fatigue, sleepiness, and mood and behavior changes.
Clinical drug development for dementia with Lewy bodies: past and present
Published in Expert Opinion on Investigational Drugs, 2019
Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh
Zonisamide is an antiepileptic being studied as adjunct therapy to levodopa for the treatment of Parkinsonism in DLB. It is currently approved in Japan as adjunct therapy to levodopa in PD patients. Results of a recent Phase 2 trial (n = 158) showed that zonisamide is effective in improving DLB-related parkinsonism, as measured by UPDRS-III, without worsening cognitive function or psychiatric symptoms [116]. The trial was conducted only in Japan and was not registered on ClinicalTrials.gov. Current study was conducted based on the positive results from previous trials that showed zonisamide improved motor symptoms and the ‘wearing-off’ phenomenon without worsening psychiatric symptoms in PD patients and a small number of DLB patients [117,118]. Zonisamide has the potential to reduce the levodopa dose needed, therefore reducing the risk of neuropsychiatric side effects. A Phase 3 trial is currently pending.